Background: In this exploratory analysis, we aim to evaluate surrogates of metastatic burden, namely number of CRMs and size of largest CRM, for their prognostic and predictive value on efficacy of maintenance therapy with 5-fluorouracil/leucovorin (FU/FA) plus panitumumab (pmab) or FU/FA alone in RAS wildtype mCRC patients treated within the PanaMa trial. Methods: Number of CRMs and size of largest CRM at baseline were determined taking into account target and non-target lesions measured by central radiological review. Median number of metastases was set as threshold (n≤/ > 10) to assess the prognostic and predictive value of CRM count on PFS and OS of maintenance therapy. A threshold of ≤/ > 50mm was set to evaluate the impact of the largest CRM on the above time-to-event endpoints. PFS and OS were expressed by Kaplan-Meier method and compared by log-rank testing. Hazard ratios (HR) with 95% CIs were estimated using Cox regression models. Results: Out of 248 patients receiving maintenance therapy, CT and MRI scans of 211 patients were centrally evaluable (FU/FA+ Pmab, n = 106; FU/FA alone, n = 105). At baseline, 50.1% of the patients were diagnosed with > 10 CRM. Median size of the largest CRM was 45 mm. Number of CRMs n≤10 was associated with favorable PFS, while both, number n≤10, and size of largest CRM ≤50mm correlated with favorable OS compared to n > 10 and size of largest CRM > 50mm, respectively. In patients with > 10 CRMs, and those with largest CRM sized > 50mm, PFS of maintenance therapy was significantly superior with FU/FA+ Pmab compared to FU/FA alone (Table). Conclusions: Metastatic burden was found to be prognostic for PFS and OS of maintenance therapy. Additionally, number and largest size of CRMs proofed predictive of PFS of maintenance therapy with Pmab, the primary endpoint of the trial. Patients with high metastatic burden at baseline appear to benefit particularly from Pmab-containing maintenance therapy. Clinical trial information: NCT01991873.

[A] FU/FA+ Pmab; [B] FU/FA alone.